Molecular Profiling–Based Precision Medicine in Cancer: A Review of Current Evidence and Challenges

Zhang, Qi; Fu, Qihan; Bai, Xueli; Liang, Tingbo

doi:10.3389/fonc.2020.532403

Cited by 26 publications

(21 citation statements)

References 68 publications

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“…Internationally published and/or presented results demonstrate the feasibility and opportunities of molecular-driven precision medicine and revealing a rate of actionable variants that justify the development of predictive biomarker-driven trials for childhood cancer. In addition to the detection of potentially druggable events, molecular profiling could also be used to identify germline mutations and change or refine diagnosis [63][64][65][66][67][68][69][70]. We will discuss these aspects separately in the next sections.…”

Section: The Development Of Precision Medicine Programs In Pediatric Oncologymentioning

confidence: 99%

The Landscape of Pediatric Precision Oncology: Program Design, Actionable Alterations, and Clinical Trial Development

Langenberg

Looze

Molenaar

2021

Cancers

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Over the last years, various precision medicine programs have been developed for pediatric patients with high-risk, relapsed, or refractory malignancies, selecting patients for targeted treatment through comprehensive molecular profiling. In this review, we describe characteristics of these initiatives, demonstrating the feasibility and potential of molecular-driven precision medicine. Actionable events are identified in a significant subset of patients, although comparing results is complicated due to the lack of a standardized definition of actionable alterations and the different molecular profiling strategies used. The first biomarker-driven trials for childhood cancer have been initiated, but until now the effect of precision medicine on clinical outcome has only been reported for a small number of patients, demonstrating clinical benefit in some. Future perspectives include the incorporation of novel approaches such as liquid biopsies and immune monitoring as well as innovative collaborative trial design including combination strategies, and the development of agents specifically targeting aberrations in childhood malignancies.

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Section: The Development Of Precision Medicine Programs In Pediatric Oncologymentioning

confidence: 99%

The Landscape of Pediatric Precision Oncology: Program Design, Actionable Alterations, and Clinical Trial Development

Langenberg

Looze

Molenaar

2021

Cancers

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“…Future molecular pathology routine testing in esophageal and gastric neoplasms may help predict overall survival and facilitate grouping patients according to their probability of response to chemoradiotherapy. Patients matched with targeted therapy have more prolonged overall survival and lower treatment costs than non-matched patients [ 80 , 81 , 82 ].…”

Section: Literature Reviewmentioning

confidence: 99%

The Role of the Heat-Shock Proteins in Esophagogastric Cancer

Tustumi

Agareno

Galletti

et al. 2022

Cells

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Heat-shock proteins (HSPs) are a family of proteins that have received considerable attention over the last several years. They have been classified into six prominent families: high-molecular-mass HSP, 90, 70, 60, 40, and small heat shock proteins. HSPs participate in protein folding, stability, and maturation of several proteins during stress, such as in heat, oxidative stress, fever, and inflammation. Due to the immunogenic host’s role in the combat against cancer cells and the role of the inflammation in the cancer control or progression, abnormal expression of these proteins has been associated with many types of cancer, including esophagogastric cancer. This study aims to review all the evidence concerning the role of HSPs in the pathogenesis and prognosis of esophagogastric cancer and their potential role in future treatment options. This narrative review gathers scientific evidence concerning HSPs in relation to esophagus and gastric cancer. All esophagogastric cancer subtypes are included. The role of HSPs in carcinogenesis, prognostication, and therapy for esophagogastric cancer are discussed. The main topics covered are premalignant conditions for gastric cancer atrophic gastritis, Barrett esophagus, and some viral infections such as human papillomavirus (HPV) and Epstein–Barr virus (EBV). HSPs represent new perspectives on the development, prognostication, and treatment of esophagogastric cancer.

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“…Precision oncology has revolutionized cancer care as evidenced by the growing list of biomarker guided targeted therapies for solid tumors including NSCLC [ 14 ]. It is therefore of clinical importance to develop a robust and affordable molecular diagnostic tool that is capable of screening multiple gene mutations in a single assay.…”

Section: Introductionmentioning

confidence: 99%

Analytical and clinical validation of a custom 15-gene next-generation sequencing panel for the evaluation of circulating tumor DNA mutations in patients with advanced non-small-cell lung cancer

Chow

Abidin²,

Kow

et al. 2022

PLoS ONE

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Background This is a pilot proof-of-concept study to evaluate the utility of a custom 15-gene circulating tumor DNA (ctDNA) panel as a potential companion molecular next-generation sequencing (NGS) assay for identifying somatic single nucleotide variants and indels in non-small-cell lung cancer (NSCLC) patients. The custom panel covers the hotspot mutations in EGFR, KRAS, NRAS, BRAF, PIK3CA, ERBB2, MET, KIT, PDGFRA, ALK, ROS1, RET, NTRK1, NTRK2 and NTRK3 genes which serve as biomarkers for guiding treatment decisions in NSCLC patients. Method The custom 15-gene ctDNA NGS panel was designed using ArcherDX Assay Designer. A total of 20 ng or 50 ng input ctDNA was used to construct the libraries. The analytical performance was evaluated using reference standards at different allellic frequencies (0.1%, 1%, 5% and parental). The clinical performance was evaluated using plasma samples collected from 10 treatment naïve advanced stage III or IV NSCLC patients who were tested for tissue EGFR mutations. The bioinformatics analysis was performed using the proprietary Archer Analysis Software. Results For the analytical validation, we achieved 100% sensitivity and specificity for the detection of known mutations in the reference standards. The limit of detection was 1% allelic frequency. Clinical validation showed that the clinical sensitivity and specificity of the assay for detecting EGFR mutation were 83.3% and 100% respectively. In addition, the NGS panel also detected other mutations of uncertain significance in 6 out of 10 patients. Conclusion This preliminary analysis showed that the custom 15-gene ctDNA NGS panel demonstrated good analytical and clinical performances for the EGFR mutation. Further studies incorporating the validation of other candidate gene mutations are warranted.

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Molecular Profiling–Based Precision Medicine in Cancer: A Review of Current Evidence and Challenges

Cited by 26 publications

References 68 publications

The Landscape of Pediatric Precision Oncology: Program Design, Actionable Alterations, and Clinical Trial Development

The Landscape of Pediatric Precision Oncology: Program Design, Actionable Alterations, and Clinical Trial Development

The Role of the Heat-Shock Proteins in Esophagogastric Cancer

Analytical and clinical validation of a custom 15-gene next-generation sequencing panel for the evaluation of circulating tumor DNA mutations in patients with advanced non-small-cell lung cancer

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